A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression
Open accessAbstract
Target identification and contact selection are known contributors to variability in efficacy across different clinical indications of deep brain stimulation surgery. A retrospective analysis of responders to subcallosal cingulate deep brain stimulation (SCC DBS) for depression demonstrated the common impact of the electrical stimulation on a stereotypic connectome of converging white matter bundles (forceps minor, uncinate fasciculus, cingulum and fronto-striatal fibers). To test the utility of a prospective connectomic approach for SCC DBS surgery, this pilot study used the four-bundle tractography 'connectome blueprint' to plan surgical targeting in 11 participants with treatment-resistant depression. Before surgery, targets were selected individually using deterministic tractography. Selection of contacts for chronic stimulation was made by matching the post-operative probabilistic tractography map to the pre-surgical deterministic tractography map for each subject. Intraoperative behavioral responses were used as a secondary verification of location. A probabilistic tract map of all participants demonstrated inclusion of the four bundles as intended, matching the connectome blueprint previously defined. Eight of 11 patients (72.7%) were responders and 5 were remitters after 6 months of open-label stimulation. At one year, 9 of 11 patients (81.8%) were responders, with 6 of them in remission. These results support the utility of a group probabilistic tractography map as a connectome blueprint for individualized, patient-specific, deterministic tractography targeting, confirming retrospective findings previously published. This new method represents a connectomic approach to guide future SCC DBS studies.
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In psychiatric surgery, advanced tractography facilitates combining brain connectomic analyses with neuromodulation interventions.
“In psychiatric surgery, advanced tractography facilitates the combination between brain connectomic analyses and neuromodulation interventions (Davidson et al., 2020; Horn et al., 2017; Riva-Posse et al., 2018)”
From Quantitative mapping of the brain’s structural connectivity using diffusion MRI tractography: A review (2022) · cites this paper as Riva-Posse et al., 2018
DBS for MDD targets the cingulate cortex or striatum (including NAc) and increases activity there and in connected anhedonia/motivation areas, plus the PFC and amygdala.
“DBS for MDD targets the cingulate cortex or the striatum, which includes the NAc, and has been shown to enhance activity in these regions and connected areas involved in anhedonia and motivation [145, 146], as well as activity in the PFC and amygdala [139].”
From Beyond the serotonin deficit hypothesis: Communicating a neuroplasticity framework of major depressive disorder (2024) · cites this paper as [146]
A polygenic sensitivity score predicts greater negative and positive responses to adverse and beneficial exposures respectively, supporting the differential-sensitivity model.
“This 'polygenic sensitivity score' predicts greater negative and positive responses to adverse and beneficial exposures respectively, supporting the differential-sensitivity model. 304”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [304]
Psychiatric disorders arise from dysfunction in distributed brain networks.
“psychiatric disorders arise from dysfunction in distributed brain networks”
From Deep brain stimulation for psychiatric disorders: From focal brain targets to cognitive networks (2021) · cites this paper as Riva-Posse et al. 2018
In a prospective open-label study, DBS implanted at a patient-specific tractographic target had an 80% response rate.
“In a prospective open-label study, DBS implanted at this patient-specific target had an 80% response rate (Riva-Posse et al. 2018).”
From Deep brain stimulation for psychiatric disorders: From focal brain targets to cognitive networks (2021) · cites this paper as Riva-Posse et al. 2018
Across indications, psychiatric DBS targets tend to be white matter tracts, especially hubs where multiple white matter bundles converge.
“A key point is that the targets for psychiatric disorders tend to be white matter tracts, especially hubs where multiple white matter bundles converge (Haber and Heilbronner 2013, Riva-Posse et al. 2018, Widge, Malone, et al. 2018).”
From Deep brain stimulation for psychiatric disorders: From focal brain targets to cognitive networks (2021) · cites this paper as Riva-Posse et al. 2018
In a prospective open-label study using individualized tractography targeting based on a group connectome blueprint, subcallosal cingulate cortex DBS produced response and remission rates at 6 months (RS: 72.7%, RM: 54.5%) and 12 months (RS: 81.9%, RM: 54.5%).
“When all patients had bilateral contacts activated that matched the four-bundle blueprint a significant and large response and remission rates was observed at 6 months (RS: 72.7%, RM: 54.5%) and 12 months (RS: 81.9%, RM: 54.5%).”
From Deep brain stimulation for depression. (2022) · cites this paper as [29]
Notable exceptions include prospective targeting of a predefined responder map of specific white matter fibers connected to the SCC and individual tractography identification of the medial forebrain bundle.
“Notable exceptions include prospective targeting of a predefined responder map of specific white matter fibers connected to the SCC [29], and the individual tractography identification of the medial forebrain bundle [72]”
From Deep brain stimulation for depression. (2022) · cites this paper as [29]
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- Authors
- Riva-Posse, P., Choi, K. S., Holtzheimer, P. E., Crowell, A. L., Garlow, S. J., Rajendra, J. K., McIntyre, C. C., Gross, R. E., & Mayberg, H. S.
- Affiliations
- Emory University (US)
- Dartmouth–Hitchcock Medical Center (US)
- University of Wisconsin–Madison (US)
- Case Western Reserve University (US)
- Venue
- Molecular Psychiatry
- Published
- 2017-04-11
- Volume
- 23
- Issue
- 4
- Pages
- 843-849
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC5636645
- OpenAlex
- W2606960287
- Cited by
- 441
- References
- 39
- Citations by year
- 2026: 33 · 2025: 39 · 2024: 43 · 2023: 60 · 2022: 47 · 2021: 70 · 2020: 53 · 2019: 43 · 2018: 42 · 2017: 11
- FWCI
- 28.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Case Western Reserve University
- National Institute of Mental Health (R01MH102238)
- Topics
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- treatment-resistant depression, probabilistic tractography, deterministic tractography, white matter bundles, forceps minor, uncinate fasciculus, cingulum, surgical targeting
- MeSH terms
- Adult, Depression, Depressive Disorder, Major, Major Depressive Disorder, Female, Gyrus Cinguli, Humans, Male, Middle Aged, Nerve Net, Pilot Projects, Prospective Studies, Retrospective Studies, Prefrontal Cortex, Deep Brain Stimulation, Diffusion Tensor Imaging, Depressive Disorder, Treatment-Resistant, Connectome, White Matter
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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